1. Field of the Disclosure
The disclosure relates generally to phosphine oxide Vitamin D precursors. More particularly, the disclosure relates to a process for preparing phosphine oxide Vitamin D precursors using an aqueous base and phase transfer catalyst for deprotonation, instead of using a metal hydride base.
2. Brief Description of Related Technology
Vitamin D analogs, such as 1α-fluoro-25-hydroxy-16-23E-diene-26,27-bishomo-20-epi-cholecalciferol, 25-dihydroxy-16-ene-23-yne-26,27-bishomo-19-nor-20-epicholecalciferol, 1α,25-dihydroxy-18-norvitamin D3, 1α,25-dihydroxy-18,19-dinorvitamin D3, 1α-fluoro-25-hydroxycholecalciferol, and 1α-fluoro-25-hydroxyergocalcifero1, are known to have pharmaceutical activity and are useful for treating various conditions, such as psoriasis and neoplastic disease.
A key phosphine oxide compound of formula 1 below is used in the efficient synthesis of such vitamin D analogs and provides the A-ring of the vitamin. Certain species of the compound of formula 1 are known to be valuable intermediates in the synthesis of the mentioned pharmacologically active vitamin D analogs (see, for example, EP Publication No. 0 808 833). The remaining species of the compound of formula 1 can be modified to be useful in the above processes or can be used for producing other vitamin D analogs.